Astrocytes in chronic active multiple sclerosis plaques express MHC class II molecules

Zeinstra, Esther; Wilczak, Nadine; Streefland, C.; Keyser, Jacques De

doi:10.1097/00001756-200001170-00018

Cited by 71 publications

(45 citation statements)

References 5 publications

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“…As constituents of the innate immune system, the myeloid-derived microglia, consequent to activation, can recruit peripheral immune cells and can provide T cells with the signals necessary for differentiation and proliferation (1,2). The neuroectodermal-derived astrocytes can also express MHC and costimulatory molecules upon activation (3,4) and share some of the immune-related functional properties of microglia. Both cell types display activated phenotypes in the CNS inflammatory lesions that characterize the putative autoimmune disease multiple sclerosis (MS) 3 (5).…”

mentioning

confidence: 99%

TLR Signaling Tailors Innate Immune Responses in Human Microglia and Astrocytes

Jack

Arbour

Manusow

et al. 2005

The Journal of Immunology

626

520

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The specific signals mediating the activation of microglia and astrocytes as a prelude to, or consequence of, CNS inflammation continue to be defined. We investigated TLRs as novel receptors mediating innate immune responses in human glial cells. We find that microglia express mRNA for TLRs 1–9, whereas astrocytes express robust TLR3, low-level TLR 1, 4, 5, and 9, and rare-to-undetectable TLR 2, 6, 7, 8, and 10 mRNA (quantitative real-time PCR). We focused on TLRs 3 and 4, which can signal through both the MyD88-dependent and -independent pathways, and on the MyD88-restricted TLR2. By flow cytometry, we established that microglia strongly express cell surface TLR2; TLR3 is expressed at higher levels intracellularly. Astrocytes express both cell surface and intracellular TLR3. All three TLRs trigger microglial activation upon ligation. TLR3 signaling induces the strongest proinflammatory polarizing response, characterized by secretion of high levels of IL-12, TNF-α, IL-6, CXCL-10, and IL-10, and the expression of IFN-β. CXCL-10 and IL-10 secretion following TLR4 ligation are comparable to that of TLR3; however, other responses were lower or absent. TLR2-mediated responses are dominated by IL-6 and IL-10 secretion. Astrocytes respond to TLR3 ligation, producing IL-6, CXCL-10, and IFN-β, implicating these cells as contributors to proinflammatory responses. Initial TLR-mediated glial activation also regulates consequent TLR expression; while TLR2 and TLR3 are subject to positive feedback, TLR4 is down-regulated in microglia. Astrocytes up-regulate all three TLRs following TLR3 ligation. Our data indicate that activation of innate immune responses in the CNS is not homogeneous but rather tailored according to cell type and environmental signal.

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mentioning

confidence: 99%

TLR Signaling Tailors Innate Immune Responses in Human Microglia and Astrocytes

Jack

Arbour

Manusow

et al. 2005

The Journal of Immunology

626

520

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“…22,63,88,89 As described previously, the initial entry of lymphocytes into the brain is suggested to be via the subarachnoid space, and/or the blood-CSF barrier, where selectins and adhesion molecules are expressed.63 Antigen presentation occurs between lymphocytes and microglial cells and also with astrocytes during neurodegenerative disease including multiple sclerosis. [90][91][92][93] Several studies have confirmed that microglial cells can express MHC-II protein and are effective antigen presenting cells. 90,91 Similarly, astrocytes also express MHC-II proteins and can act as antigen presenting cells.…”

Section: Movement Of Lymphocytes In and Out Of The Cnsmentioning

confidence: 99%

“…90,91 Similarly, astrocytes also express MHC-II proteins and can act as antigen presenting cells. 92,93 Along with these cells, dendritic cells and macrophages, the professional antigen presenting cells, also help in antigen presentation to lymphocytes in the perivascular space. 90 Alternatively, it has also been shown that neurons interact with T cells via B7 ligand in the absence of MHC-II molecules as they do not express MHC-II molecules.…”

Section: Movement Of Lymphocytes In and Out Of The Cnsmentioning

confidence: 99%

Is Central Nervous System an Immune-Privileged Site?

Shrestha

Millington

Brewer

et al. 2014

Kathmandu Univ. Med. J.

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The central nervous system (CNS) was once considered to be an immune-privileged area. However, increasing evidence shows that the central nervous system is not an immune-privileged but is an active surveillance site. There is a bi-directional communication between the central nervous system and immune system. Normally, immune cells migrate into the central nervous system microenvironment through choroid plexus and interact with the central nervous system resident cells through either through neuromediators or immunomediators. This finding has led to a significant interest in neuroimmunological interactions and investigation onto the role of the immune system in the pathology of various neurological disorders and examine whether it can be targeted to produce novel therapeutic strategies.

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“…In murine experimental autoimmune encephalomyelitis (EAE), an established animal model of multiple sclerosis, astrocyte hypertrophy coincided with manifestation of axonal damage (Wang et al, 2005). Astrocytes in multiple sclerosis plaques produce IL-6 (Okuda et al, 1998), lack -2 adrenergic receptors, and potentially serve as antigen-presenting cells (Zeinstra et al, 2000b), thus facilitating Tcell invasion and activation. Repeated exposure of these astrocytes to inflammatory cytokines triggers unregulated inflammatory responses and increased noradrenalin levels, leading to focal areas of myelin and axonal damage (De Keyser et al, 1999;Zeinstra et al, 2000a).…”

Section: Multiple Sclerosismentioning

confidence: 99%